贵州医科大学学报

2020, v.45;No.235(04) 396-401+407

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血管性血友病因子在感染性关节炎发生发展中的作用
Role of Von Willebrand Factor in Development of Infectious Arthritis

胡智成;金涛;费樱;
HU Zhicheng;JIN Tao;FEI Ying;College of Medical Laboratory,Guizhou Medical University;Center of Clinical Laboratory,the Affiliated Hospital of Guizhou Medical University;Centre of Medical Research on Rheumatism and Inflammation,University of Gothenburg;

摘要(Abstract):

目的:研究血管性血友病因子(VWF)在感染性关节炎发生发展中的作用。方法:采用金黄色葡萄球菌尾静脉注射方法建立小鼠感染性关节炎模型,分为两个阶段实验;第一阶段研究去除VWF对感染性关节炎的影响,使用7只VWF基因敲除小鼠作为实验组,7只NMRI小鼠作为对照组,于建模后第3、4、7、10天观察小鼠的一般情况,计算体质量变化率,评定关节炎指数和关节炎频率;第二阶研究VWF对感染性关节炎的影响,使用NMRI小鼠25只,随机分为Minirin组(n=13)和PBS组(n=12),Minirin组于建模前1 h腹腔注射醋酸去氨加压素(DDAVP),PBS组注射等量PBS处理,分别于建模后第3、4、7、10天观察小鼠的一般情况,称量并计算小鼠的体质量变化率和存活率,评定关节炎指数、关节炎频率和多关节炎频率,计算肾脏肿胀指数及肾脏进行细菌承载量,实验结束时取两组小鼠关节进行影像学检查,并评估骨损伤指数和骨损伤频率;于实验第10天处死小鼠后收集血清检测白细胞介素-6(IL-6)和角质形成细胞衍生的细胞因子(KC)水平。结果:第一阶段实验,实验组和对照组小鼠的体质量变化率比较,差异无统计学意义(P <0. 05);从实验第3天起,实验组小鼠关节炎指数和关节炎频率均明显低于对照组,差异具有统计学意义(P <0. 05,P <0. 01);第二阶段实验,两组小鼠在感染后第3天开始出现不同程度的关节炎症状,关节及皮肤表面出现红肿等炎症变化;影像学显示,Minirin组和PBS组均出现骨损伤;与PBS组比较,Minirin组小鼠存活率、关节炎指数、关节炎频率、多关节炎频率、肾脏脓肿程度、肾脏细菌承载量、骨损伤指数、骨损伤频率以及小鼠血清中IL-6、KC水平比较,差异无统计学意义(P> 0. 05)。结论:VWF减少是影响金黄色葡萄球菌感染性关节炎的关键因素,DDAVP对关节炎的发生发展无明显作用。
Objective: To explore the effects of von willebrand factor( VWF) on the development of infectious arthritis. Methods: The infectious arthritis model of mice was established by means of Staphylococcus aureus tail vein injection,which was divided into two stages. Effect of removal VWF on infectious arthritis was studied at the first stage,and 7 VWF knockout mice were used as experimental group and 7 NMRI mice as control group. On the 3~(rd),4~(th),7~(th)and 10 thdays after modeling,the general condition of mice was observed,the weight change rate was calculated,and the arthritis index and arthritis frequency were evaluated. Effect of VWF on infectious arthritis was studied at the second stage,and twenty-five NMRI mice were randomly divided into Minirin groups( n = 13) and PBS groups( n = 12). The Minirin group was treated with intraperitoneal injection of deaminopressin acetate( DDAVP) 1 hour before modeling,and PBS group was treated with the equivalent injection.On the 3~(rd),4~(th),7~(th)and 10 thdays after modeling,the general conditions of mice were observed,and the weight change rate and survival rate of mice were measured and calculated. The arthritis index,arthritis frequency and multi-articular frequency were evaluated,and the swelling index of kidney and the bacterial carrying capacity of kidney were calculated. At the end of the experiment,two groups of mouse joints were examined by imaging,and bone injury index and frequency were evaluated. The serum levels of interleukin-6( IL-6) and keratinocyte-derived cytokines( KC) were collected after mice were sacrificed on the 10 th day of the experiment. Results: There was no significant difference in weight change rate between experimental group and control group in the first stage experiment( P <0. 05). From the third day of the experiment,the arthritis index and arthritis frequency of the mice in the experimental group were significantly lower than those in the control group,and the difference was statistically significant( P < 0. 05,P < 0. 01). In the second stage of the experiment,the two groups of mice began to develop different degrees of inflammation in the joints on the 3 rd day after infection,and there were inflammatory changes such as redness and swelling on the joints and skin surfaces. Imaging showed bone damage in Minirin and PBS groups. There was no significant difference in survival rate,arthritis index,arthritis frequency,polyarthritis frequency,kidney abscess degree,kidney bacterial load,bone injury index,bone injury frequency and the level of IL-6 and KC in mouse serum compared with PBS group( P > 0. 05). Conclusion: The decrease of VWF is the key factor affecting the infectious arthritis of Staphylococcus aureus,and DDAVP has no obvious effect on the development of arthritis.

关键词(KeyWords): 葡萄球菌,金黄色;毒力因子类;小鼠;醋酸去氨加压素;血管性血友病因子;感染性关节炎
Staphylococcus aureus;virulence factors;mice;deaminopressin acetate(DDAVP);von willebrand factor(VWF);infectious arthritis

Abstract:

Keywords:

基金项目(Foundation): 国家自然科学基金(81460334);; 贵州省科技创新人才团队[黔科合平台人才(2019)5610]

作者(Author): 胡智成;金涛;费樱;
HU Zhicheng;JIN Tao;FEI Ying;College of Medical Laboratory,Guizhou Medical University;Center of Clinical Laboratory,the Affiliated Hospital of Guizhou Medical University;Centre of Medical Research on Rheumatism and Inflammation,University of Gothenburg;

Email:

DOI: 10.19367/j.cnki.1000-2707.2020.04.005

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